Association of complement factor H Y402H polymorphism and age-related macular degeneration in Brazilian patients

Purpose: The aim of this study was investigate the association between complement Factor H polymorphism (Y402H) and age-related macular degeneration (AMD) in Brazilian patients. Methods: Patients with AMD aged 50 or more and age-matched healthy controls were enrolled in the study. Genomic DNA was isolated from leucocytes of patients and controls; the Y402H polymorphism of complement Factor H gene (CFH) was determined by polymerase chain reaction directed sequencing. Results: The frequency of 1277C allele of Factor H was 56.30% in patients with AMD compared with 36.51% in controls (p-value = 0.001). The genotypic distribution differed significantly between the two groups (1277CC 36.98%, 1277CT 38.65% and 1277TT 24.37% for AMD group; 1277CC 13.16%, 1277CT 46.71% and 1277TT 40.13% for controls, p-value = 0.001). The odds ratio for patients with AMD carrying only one 1277C allele was 1.36 and for those carrying two 1277C alleles was 4.63, when compared to the control group. Conclusions: These results suggest the Y402H polymorphism of CFH is a risk factor to the development of AMD in Brazilian patients. This is in accordance with findings from the majority of previous study population in Europe and North American.

Functional Characterization of LcpA, a Surface-Exposed Protein of Leptospira spp. That Binds the Human Complement Regulator C4BP

We have previously shown that pathogenic leptospiral strains are able to bind C4b binding protein (C4BP). Surface-bound C4BP retains its cofactor activity, indicating that acquisition of this complement regulator may contribute to leptospiral serum resistance. In the present study, the abilities of seven recombinant putative leptospiral outer membrane proteins to interact with C4BP were evaluated. The protein encoded by LIC11947 interacted with this human complement regulator in a dose-dependent manner. The cofactor activity of C4BP bound to immobilized recombinant LIC11947 (rLIC11947) was confirmed by detecting factor I-mediated cleavage of C4b. rLIC11947 was therefore named LcpA (for leptospiral complement regulator-acquiring protein A). LcpA was shown to be an outer membrane protein by using immunoelectron microscopy, cell surface proteolysis, and Triton X-114 fractionation. The gene coding for LcpA is conserved among pathogenic leptospiral strains. This is the first characterization of a Leptospira surface protein that binds to the human complement regulator C4BP in a manner that allows this important regulator to control complement system activation mediated either by the classical pathway or by the lectin pathway. This newly identified protein may play a role in immune evasion by Leptospira spp. and may therefore represent a target for the development of a human vaccine against leptospirosis.

A new model of outbred genetically selected mice which present a strong acute inflammatory response in the absence of complement component C5

Mice selected for a strong (AIRmax) or weak (AIRmin) acute inflammatory response present different susceptibilities to bacterial infections, autoimmune diseases and carcinogenesis. Variations in these phenotypes have been also detected in AIRmax and AIRmin mice rendered homozygous for Slc11a1 resistant (R) and susceptible (S) alleles. Our aim was to investigate if the phenotypic differences observed in these mice was related to the complement system. AIRmax and AIRmin mice and AIRmax and AIRmin groups homozygous for the resistance (R) or susceptibility (S) alleles of the solute carrier family 11a1 member (Slc11a1) gene, formerly designated Nramp-1. While no difference in complement activity was detected in sera from AIRmax and AIRmin strains, all sera from AIRmax Slc11a1 resistant mice (AIRmax(RR)) presented no complement-dependent hemolytic activity. Furthermore, C5 was not found in their sera by immunodiffusion and, polymerase chain reaction and DNA sequencing of its gene demonstrated that AIRmax(RR) mice are homozygous for the C5 deficient (D) mutation previously described in A/J. Therefore, the C5D allele was fixed in homozygosis in AIRmax(RR) line. The AIRmax(RR) line is a new experimental mouse model in which a strong inflammatory response can be triggered in vivo in the absence of C5.

Immune Evasion of Leptospira Species by Acquisition of Human Complement Regulator C4BP

Leptospirosis is a spirochetal zoonotic disease of global distribution with a high incidence in tropical regions. In the last 15 years it has been recognized as an important emerging infectious disease due to the occurrence of large outbreaks in warm-climate countries and, occasionally, in temperate regions. Pathogenic leptospires efficiently colonize target organs after penetrating the host. Their invasiveness is attributed to the ability to multiply in blood, adhere to host cells, and penetrate into tissues. Therefore, they must be able to evade the innate host defense. The main purpose of the present study was to evaluate how several Leptospira strains evade the protective function of the complement system. The serum resistance of six Leptospira strains was analyzed. We demonstrate that the pathogenic strain isolated from infected hamsters avoids serum bactericidal activity more efficiently than the culture-attenuated or the nonpathogenic Leptospira strains. Moreover, both the alternative and the classical pathways of complement seem to be responsible for the killing of leptospires. Serum-resistant and serum-intermediate strains are able to bind C4BP, whereas the serum-sensitive strain Patoc I is not. Surface-bound C4BP promotes factor I-mediated cleavage of C4b. Accordingly, we found that pathogenic strains displayed reduced deposition of the late complement components C5 to C9 upon exposure to serum. We conclude that binding of C4BP contributes to leptospiral serum resistance against host complement.

Deficiency of the human complement regulatory protein factor H associated with low levels of component C9

We identified a 4-year-old Brazilian boy from a family of Japanese descent and history of consanguinity, who suffered from severe recurrent pneumonia. He carries factor H (FH) deficiency associated with reduced levels of component C9 and low serum levels of C3 and factor B. His mother also presented low levels of these proteins and factor I, while his father and sister had only lower levels of FH. Western blot assays confirmed the complete absence of FH and FHL-1 polypeptides in this patient. Sequencing of the proband`s FH cDNA revealed a homozygous G453A substitution, encoding an Arg(127)His change. His mother, father and sister are heterozygous for this substitution. Despite the absence of FH in the plasma, this protein was detected in the patient`s fibroblasts, suggesting that Arg(127) may be important for FH secretion. Low concentrations of C9 were detected in the proband serum but no mutations in the patient`s C9 gene or promoter have been identified, suggesting that this is a consequence of uncontrolled complement activation and high C9 consumption.

Skipping of exon 30 in C5 gene results in complete human C5 deficiency and demonstrates the importance of C5d and CUB domains for stability

The deficiency of complement C5 is rare and frequently associated with severe and recurrent infections, especially caused by Neisseria spp. We observed the absence of component C5 in the serum of 3 siblings from a Brazilian family with history of consanguinity. The patients had suffered from recurrent episodes of meningitis and other less severe infections. Sera from these patients were unable to mediate hemolytic activity either by the classical or alternative pathways and presented extremely low levels of C5 protein (13, 0.9 and 1.0 mu g/ml-normal range: 45-190 mu g/ml). Hemolytic activity could be restored by the addition of purified C5 to deficient serum. Sequencing of sibling C5 cDNA revealed a homozygous 153 bp deletion that corresponds precisely to exon 30. The parents carried the same deletion but only in one allele. Sequencing of the corresponding region in the genomic DNA revealed a C to C substitution within intron 30 and, most significantly, the substitution of GAG(4028) for GAA(4028) at the 3` end of exon 30 which is most likely responsible for skipping of exon 30. The resulting in-frame deletion in the C5 mRNA codes for a mutant C5 protein lacking residues 1289-1339. These residues map to the CUB and C5d domains of the C5 alpha chain. This deletion is expected to produce a non-functional and unstable C5 protein which is more susceptible to degradation. (C) 2009 Published by Elsevier Ltd.

Scriptural Archeology: Excavating the Presence of Women in the Torah

Women's roles in religious history have been traditionally described in terms of their relation and value to men. The normative religious texts provide an androcentric perspective on the gender relationships within the early community, the growth of Judaism in "Jacob's House" and the monotheistic worship of God. Yet these literary representations omit an entire half of the experience of the Jewish community: the perspective and participation of women. As Judith Plaskow argues extensively in Standing Again at Sinai, women are defined not in her own terms or in her own voice, but by her relationship and value to men through the androcentric vocabulary of the Torah. This statement is textually illustrated by the authorial and editorial presentation of women and their place in ancient Israelite society in the Torah. As Judaism grew increasingly androcentric in its leadership, women were increasingly reduced to marginal figures in the community by authorial and editorial revisions. Yet the participation of women of ancient Israel is not lost. Instead, the presence of women is buried beneath the androcentric presentation of the early Judaic community, waiting to be excavated by historical and scriptural examination. The retelling of the past is influenced by the present; memory is not static but takes on different shapes depending on the focus of concentration. However, tradition greatly influences the interpretation of religious history as well. In the book of Genesis, the literature emphasizes the divine appointment of male figures such as Abraham the father of the covenant and Jacob who is renamed and claimed by God as "Israel," placing them at the center of Jewish history. As a result, the other figures in these biblical narratives are described in relation to the patriarchs, those male bearers of the covenant, by their service or their value to him. Women are at the bottom of this hierarchy. Although female figures of exceptional quality are noted in later chronicles, such as Ruth, Deborah and Miriam, it is the very nature of their exception that highlights the androcentric editorial focus of the Torah. I agree with Peggy Day, whose own scriptural examination in Gender and Difference in Ancient Israel, makes the important distinction between the literary representation and the reality of ancient Israelite culture: they are not coextensive nor equivalent. Although the text represents the culture of ancient Israel as male dominated from the time of Abraham, this presentation omits the perspective of half of the population-the women. By beginning at the point of realization that women did exist and were active in their culture, and placing aside the androcentric perspective of the text and its editors, the reality of women's place in ancient Israel may be determined. Through this new perspective, the women of the Torah will emerge as the archetypes of strength, leadership and spiritual insight to provide Jewish women of the present with female, ancestral role models and a foundation for their gender's heritage, a more complete understanding of the partial record of Jewish history recorded in the Torah. Those stories that appear as the exception of women's presence will unveil an exceptional presence. As Tamar Frankiel eloquently states in The Voice of Sarah, "the women we call our 'Mothers'-Sarah, Rivkah (Rebekah), Rachel, and Leah-are not merely mothers, any more than the 'Fathers'-Abraham, Isaac and Jacob-are merely fathers "(Frankiel 5).

Comunicação, Saúde e Pluralidade: novos olhares e abordagens em pauta

Propomos um passeio acadêmico por 11 textos de pesquisadores afinados com a temática Health Communication na versão brasileira, mostrando a riqueza de assuntos, metodologias e enfoques que os estudos dessa área permitem na academia. Trata-se de uma visão multidisciplinar, às vezes com a Comunicação no foco principal, por outras a Saúde no estetoscópio dos pesquisadores.

Relações iatrogênicas na instituição hospitalar: uma abordagem psicológica

Esta pesquisa aborda o estudo do desempenho do psicólogo e as relações iatrogênicas na Instituição Hospitalar. Foi realizada durante os anos de 1989 e 1990 uma pesquisa-ação, numa unidade hospitalar da rede oficial de Saúde, do Estado do Rio de Janeiro. Como fundamentação teórica, o estudo apoiou-se nas teses, entre outras, de Renê Barbier, Ivan Illich, H. Ferrari, Isaac Luchina e Michael Balint para facilitar a compreen são do significado da Instituição, das relações iatrogênicas e da relação médico-paciente. Trabalhando numa equipe de profissionais ligados ao Serviço de Psicossomática desenvolvemos atividades que en volvessem aspectos psicológicos psicodinâmicos da relação as sistencial entre a equipe interdisciplinar e o paciente, enfocando mais intimamente o papel do médico no seu ATO de assistir. Analisando o Hospital Geral, enquanto Instituição e todas as relações que ali se efetivavam procurou a pesquisa identificar os discursos e as práticas que perpassavam os diferentes segmentos da própria Instituição. A abordagem dialética foi o instrumental básico deste trabalho e o estudo de casos clínicos apresentados ofereceu-nos além de uma reflexão sobre o cotidiano hospitalar, uma proposta de ação oriunda da análise dos mesmos. Dos quatro casos estudados, dois relativos a crianças e dois a adultos (atendidos na enfermaria de cirurgia infantil e no ambulatório do Serviço de Psicossomitica, respectivamente), tornou-se mais evidente que a atuação do psicólogo deve ser encarada não como uma alternativa de trabalho, mas sim como função imprescindível no desenvolvimento da relação médico-paciente.

Mediação no palco do pequeno grupo de trabalho: uma tentativa de coompreensão do conflito e seus rumos alternativos através da variável tempo

Do ponto de vista formal, este trabalho caracteriza-se por uma reflexão contínua a respeito dos encontros e desencontros humanos que, neste momento, dirige-se para uma sistematização que permita sua legibilidade por terceiros. Contribuir para a construção de uma Psico-Sociologia do Amor, através do desenvolvimento de uma caminhada em busca de maior compreensão para o conflito no Pequeno Grupo Humano de Trabalho, tentando delinear um quadro revelador de elementos chave no processo de cisão-coesão do mesmo.

Língua Brasileira de Sinais – Libras: uma introdução

O item não apresenta o texto completo, pois está passando por revisão editorial

Presence of antibodies against Leishmania chagasi in haemodialysed patients

SOUZA,Roberto Mascarenhas et al.Presence of antibodies against Leishmania chagasi in haemodialysed patients.Transactions of the Royal Society of Tropical Medicine and Hygiene,v. 103, p.749-751, 2009.